METABOLIC PRODUCTS 



289 



belonging to other genera also produce penicillin. Sterile culture condi- 

 tions must be maintained at all times, as penicillin is rapidly destroyed 

 by the enzyme, penicillinase, which is excreted by many bacteria. Peni- 

 cillin is extracted from the "fermentation" liquid, or penicillin beer, 

 either by extraction at pH 2.0 to 2.5 with water-immiscible solvents such 



S 



R— 



— CO— NH— CH- 

 0=0— 



-CH C— (CH3)2 



-N CH— COOH 



Type formula of the penicillins 



as amyl acetate, or by adsorption on activated carbon. The extraction 

 must be carried out quickly from acid solutions, owing to the instability 

 of penicillin under these conditions. Penicillin forms crystalline salts 

 with the alkali metals. The sodium salt is usually produced. 



Table 51. Names and American and British-type Designations of Four 



Naturally Occurring Penicillins 



Penicillin, as produced by P. chrysogenum, is a mixture of related com- 

 pounds. The ratios among the various penicillins depends upon the 

 isolate and conditions used. By the use of suitable precursors the yield 

 of the desired compound, penicillin G, is greatly increased. This is 

 desirable because penicillin G salts crystallize well and are most useful 

 in medicine. The type formula for the penicillins is shown below. The 

 precursors used for the production of penicillin G are related to phenyl- 

 acetic acid. Many other penicillins are known, some of which are pro- 

 duced only in the presence of precursors which do not occur in nature 

 (Behrens, 1949). 



The growth of the penicillin industry in the United States is shown by 

 the production figures in Table 52. 



Penicillin is chiefly active against Gram-positive bacteria. A few 

 important Gram-negative pathogens, including Neisseria gonorrhoeae and 

 Treponema pallidum, are controlled by penicillin. Penicillin is not active 

 against acid-fast bacteria or fungi. Many bacteria may become resist- 

 ant, or fast, to penicillin. Whether natural selection or mutation or both 

 are involved in this phenomenon is uncertain. The morphology and 



